ArticleMolecular and cellular biology2001
NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers.
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Who cites it
235 citing papers in PubMed, 575 citations in OpenAlex.
- Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies.International journal of molecular sciences · 2026Review
- Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α.EMBO reports · 2026Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Differential RELA and GR recruitment to the BIRC3/BIRC2 locus: Molecular insight as to combinatorial regulation by proinflammatory cytokines and glucocorticoid.Molecular pharmacology · 2025Article
- Enhancement of Tumor Necrosis Factor-α-Mediated Hepatic Apoptosis and Liver Injury by Hepatitis B Virus Surface Antigen.The American journal of pathology · 2025Article
- PARP12-mediated mono-ADP-ribosylation as a checkpoint for necroptosis and apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- FLIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Recent advances in the role of gasotransmitters in necroptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Biological Functions and Clinical Implications of CFLAR: From Cell Death Mechanisms to Therapeutic Targeting in Immune Regulation.Journal of inflammation research · 2025Review
- Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.Nature communications · 2024Article
- Regulation of RIPK1 Phosphorylation: Implications for Inflammation, Cell Death, and Therapeutic Interventions.Biomedicines · 2024Review
- Beyond Death: Unmasking the Intricacies of Apoptosis Escape.Molecular diagnosis & therapy · 2024Review
- Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.Nature communications · 2024Article
- Novel insights into double-stranded RNA-mediated immunopathology.Nature reviews. Immunology · 2024Review
- Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells.Cell death & disease · 2024Review
- Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.Frontiers in molecular neuroscience · 2024Article
- A computational model of the DNA damage-induced IKK/ NF-κB pathway reveals a critical dependence on irradiation dose and PARP-1.iScience · 2023Article
- Review
- Oxidative Stress Induced by Selenium Deficiency Contributes to Inflammation, Apoptosis and Necroptosis in the Lungs of Calves.Antioxidants (Basel, Switzerland) · 2023Article
- Selenium Deficiency-Induced Oxidative Stress Causes Myocardial Injury in Calves by Activating Inflammation, Apoptosis, and Necroptosis.Antioxidants (Basel, Switzerland) · 2023Article
175 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The caspase 8 homologue FLICE-inhibitory protein (cFLIP) is a potent negative regulator of death receptor-induced apoptosis. We found that cFLIP can be upregulated in some cell lines under critical involvement of the NF-kappaB pathway, but NF-kappaB activation was clearly not sufficient for cFLIP induction in all cell lines. Treatment of SV80 cells with the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG-132) or geldanamycin, a drug interfering with tumor necrosis factor (TNF)-induced NF-kappaB activation, inhibited TNF-induced upregulation of cFLIP. Overexpression of a nondegradable IkappaBalpha mutant (IkappaBalpha-SR) or lack of IkappaB kinase gamma expression completely prevented phorbol myristate acetate-induced upregulation of cFLIP mRNA in Jurkat cells. These data point to an important role for NF-kappaB in the regulation of the cFLIP gene. SV80 cells normally show resistance to TNF-related apoptosis-inducing ligand (TRAIL) and TNF, as apoptosis can be induced only in the presence of low concentrations of cycloheximide (CHX). However, overexpression of IkappaBalpha-SR rendered SV80 cells sensitive to TRAIL-induced apoptosis in the absence of CHX, and cFLIP expression was able to reverse the proapoptotic effect of NF-kappaB inhibition. Western blot analysis further revealed that cFLIP, but not TRAF1, A20, and cIAP2, expression levels rapidly decrease upon CHX treatment. In conclusion, these data suggest a key role for cFLIP in the antiapoptotic response of NF-kappaB activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.